Interventions for the management of post COVID-19 condition (long COVID): Protocol for a living systematic review & network meta-analysis (preprint)

Background: Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia, and impaired cognitive function, termed post COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice. Objective To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID. Methods Eligible trials will randomize adults with long COVID, to pharmacologic or non-pharmacologic interventions, placebo, sham, or usual care. We will identify eligible studies by searches of MEDLINE, EMBASE, CINAHL, PsycInfo, AMED, and CENTRAL, from inception, without language restrictions. Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest, and assess risk of bias. Our outcomes of interest will include fatigue, pain, post-exertional malaise, changes in education or employment status, cognitive function, mental health, dyspnea, quality of life, patient-reported physical function, recovery, and serious adverse events. For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The GRADE approach will guide our assessment of the certainty of evidence. We will update our living review biannually, upon the publication of a seminal trial, or when new evidence emerges that may change clinical practice. Conclusion This living systematic review and network meta-analysis will provide comprehensive, trustworthy, and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline producing organizations to inform their recommendations.

Prevalence and factors influencing long COVID among primary healthcare workers after epidemic control policy adjustment in Jiangsu, China (preprint)

Objective: This study aims to evaluate the prevalence of long COVID infections and their influencing factors among primary HCWs after epidemic control policy adjustment in Jiangsu. Methods: : A self-designed questionnaire was administered through on-site surveys among primary HCWs in five counties and districts within Jiangsu Province from July 4 to July 20, 2023. Results: : The prevalence of long COVID among primary HCWs stood at 12.61% (95% confidence interval (CI) of 11.67%-13.55%). The most common long COVID symptoms were hypomnesia (4.90%), sleep difficulties (2.73%), fatigue (2.35%), disturbances in the reproductive system (1.93%), hair loss (1.85%), and myalgia/arthralgia (1.51%). Multivariate logistic regression revealed that older age groups (30-45 years (adjusted odds ratios (aOR) =1.93, 95%CI: 1.44-2.58), 45-60 years (aOR=2.82, 95%CI: 2.07-3.84)), females (aOR=1.26, 95%CI: 1.03-1.55), and higher work stress (high stress (aOR=1.52, 95%CI: 1.24-1.86), extremely high stress (aOR=1.37, 95%CI: 1.03-1.82)) were more prone to long COVID. Conversely, individuals with educational attainment below the bachelor’s degree (aOR=0.67, 95%CI: 0.55-0.82) and those who received four or more doses of the COVID-19 vaccine (aOR=0.55, 95%CI: 0.33-0.92) were at a reduced risk. Conclusion: To mitigate the incidence of long COVID, healthcare providers and authorities should implement effective measures, including optimizing work-rest schedules and actively advocating for vaccination.

Tracking Persistent Symptoms in Scotland (TraPSS): A Longitudinal Prospective Cohort Study of COVID-19 Recovery After Mild Acute Infection (preprint)

Background: COVID-19 disease results in disparate responses between individuals and has led to the emergence of Long-COVID, characterized by persistent and cyclical symptomology. To understand the complexity of Long-COVID, the importance of symptom surveillance and prospective longitudinal studies is evident. Methods: A 9-month longitudinal prospective cohort study was conducted within Scotland (n=287), using a mobile app to determine the proportion of recovered individuals, those with persistent symptoms, common symptoms, and associations with gender and age. Results: 3.1% of participants experienced symptoms at month 9, meeting the criteria for Long-COVID, as defined by the NICE terminology. Fatigue, cough, and muscle pain were the most common symptoms at baseline, with fatigue persisting the longest, while symptoms like cough improved rapidly. Older age increased the likelihood of reporting pain and cognitive impairment. Female gender increased the likelihood of headaches and post-exertional malaise (PEM), and increased recovery time from fatigue and PEM. Conclusions: The majority of people fully recover from acute COVID-19, albeit often slowly. Age and gender play a role in symptom burden and recovery rates, emphasizing the need for tailored approaches to Long-COVID management. Further analysis is required to determine the characteristics of the individuals still reporting ongoing symptoms months after initial infection to identify risk factors and potential predictors for the development of Long-COVID.

Clinical features and outcomes in kidney transplant recipients with COVID-19 pneumonia: a single center retrospective cohort study (preprint)

Objective This retrospective cohort study aimed to assess the clinical characteristics, treatment outcomes, and short-term prognosis of kidney transplant recipients (KTRs) with concurrent coronavirus disease 2019 (COVID-19) pneumonia.Methods KTRs with COVID-19 pneumonia who were admitted to our hospital from December 28, 2022, to March 28, 2023 were included in the study, and their clinical symptoms, response to antiviral medications, and short-term prognosis were analyzed.Results A total of 64 KTRs with initial diagnosis of COVID-19 pneumonia were included in this study. The primary symptoms were fever, cough, and myalgia, with an incidence of 79.7%, 89.1%, and 46.9%, respectively. The administration of antiviral drugs (paxlovid or molnupiravir) within 1–5 days and for over 5 days demonstrated a statistically significant reduction in viral shedding time compared to the group without antiviral medication (P = 0.002). Both the paxlovid and molnupiravir treatment groups exhibited a significantly shorter duration of viral shedding time in comparison to the group without antiviral drugs (P = 0.002). After 6 months of recovery, there was no significantly negative impact on transplant kidney function (P = 0.294).Conclusion Fever, cough, and myalgia remain common initial symptoms of concurrent COVID-19 pneumonia in KTRs. The earlier use of antiviral drugs (the paxlovid or molnupiravir) is associated with better therapeutic outcomes. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had limited impact on short-term renal function of the KTRs with concurrent moderate or severe COVID-19 pneumonia.

IMPACT OF PANDEMIC ON COVID-19 QUALITY OF LIFE AND EFFECTING FACTORS AMONG ADULTS WITH LONG COVID: FAMILY HEALTH CENTERS BASED STUDY (preprint)

Aim: The aim of the study was to evaluate impact of pandemic on COVD-19 quality of life and effecting factors among adults wıth long COVID. Methods: The study included 440 individuals applying at family health centers for any reason. Participants were asked to complete a survey after their written consent was received. The survey consisted of two parts: the first related to socio-demographic information; the second including “COVID-19 Quality of Life Scale” and the “Perception Health Scale” . Mean, median, Kruskal Wallis and Mann-Whitney U tests and Sperman Correlation analysis were used in analysis. Results: Of the participants, 40.9% were male, 59.1% were female as well as 33.2% had at least one long COVID symptoms, 44.5% were reported that symptoms continued for 1-3 months. In addition, the median age was 41 years, the body mass index was 24.6 kg/m2. The median time since first infected was 7 month. The median COV19-QoL and Perception of Health Scale scores were 3.0 and 40.0 respectively. Among the prolonged COVID symptoms, fatigue/tiredness was shown with 53.2%. Other common symptoms were muscle pain (27.1%), headache/dizziness (24.1%), difficulty thinking or concentrating (20.9%), difficulty in breathing and heart palpitation (20.0%). The COV19-QoL median score significantly differed by education level, existing chronic conditions, COVID-19 treatment type, number of experienced long COVID symptoms and continuation of the symptoms p<0.05. There was significant correlation between COV19-QoL and age, time since first infected and perceived health score (p<0.05) . Conclusion: Aging, low education, existing chronic conditions, hospitalization, number of long symptoms, continuation of symptoms, and perception of health were risky factors for impact of the pandemic on COVID-19 quality of life. Specific rehabilitation services and programmes seems to be urgent need in overcoming this issue and to improve health. Key words: Long COVID, COVID-19, quality of life, adults, family health

Menstrual Symptom Disorders After COVID-19 in Relation To Anxiety and Long COVID Symptoms (preprint)

Aim: and objectives: Coronavirus disease (COVID-19) can affect the menstrual cycle and menstrual volume. We aimed to examine the changes in menstrual symptoms of women who had recovered from COVID-19 and determine the factors affecting these changes. Methods: A questionnaire, prepared using Google Forms, was completed online in May 18-31, 2021 by 180 women (26.08±6.62 years) who had recovered from COVID-19. Menstrual symptoms, menstrual pain severity, fatigue severity and anxiety levels of the participants were assessed with Menstrual Symptom Questionnaire (MSQ), Visual Analogue Scale (VAS) and Fatigue Severity Scale (FSS), Coronavirus Anxiety Scale (CAS), respectively. Results: Post-COVID-19 individuals’ MSQ total scores and subgroup scores, FSS scores and menstrual pain showed a statistically significant increase compared to pre-COVID-19 (p < 0.001 for all). Multiple linear regression analysis identified age at menarche and change in FSS and VAS scores as significant contributors to 38.4% of the variance explained in the significant regression for change in MSQ score (F (3.176) = 38.23, p < 0.001). Individuals with prolonged fatigue, muscle–joint pain and dyspnea symptoms showed increased MSQ total scores (p = 0.006, p = 0.009, p = 0.046 respectively) and negative effects/somatic complaints subgroup scores (p = 0.004, p = 0.002, p = 0.017 respectively). Also, individuals with prolonged gastrointestinal symptoms showed increased pain symptoms (p = 0.029) and coping methods subgroup scores (p = 0.002), while those with prolonged muscle and joint pain showed increased coping methods (p = 0.022) subgroup scores. Conclusion: In this study, we observed worsened menstrual symptoms, fatigue, and menstrual pain severity in women recovered from COVID-19. In addition, age at menarche and fatigue and menstrual pain scores differences after COVID-19 were determiners of the changes in menstrual symptoms. Menstrual symptoms were more severe in women who have prolonged fatigue, dyspnea, muscle–joint pain, and gastrointestinal symptoms.

IMPACT OF COVID-19 PANDEMIC ON QUALITY OF LIFE AND EFFECTING FACTORS AMONG ADULTS WITH LONG COVID: FAMILY HEALTH CENTERS BASED STUDY (preprint)

Background: Long COVID are the uninterpretable symptoms of COVID-19. However, quality of life and other factors among COVID-19 survivors remain less clear. Objectives: The aim of the study was to evaluate impact of COVID-19 pandemic on quality of life and effecting factors among adults with long COVID. Design and Setting: This cross-sectional study included 440 individuals applying at family health centers for any reason. Methods: The survey consisted of two parts: the first related to socio-demographic information; the second including “COVID-19 Quality of Life Scale”and the “Perception Health Scale”. Results: Of the participants, 40.9% were male, 59.1% were female as well as 33.2% had at least one long COVID symptoms. The median COV19-QoLand Perception of Health Scale scores were 3.0 and 40.0 respectively. Among the prolonged COVID symptoms, fatigue/tiredness was shown with 53.2%. Other common symptoms were muscle pain (27.1%), headache/dizziness (24.1%), difficulty thinking or concentrating (20.9%), difficulty in breathing and heart palpitation (20.0%). The COV19-QoL median score significantly differed by education level, existing chronic conditions, COVID-19 treatment type, number of experienced long COVID symptoms and continuation of the symptoms p<0.05. There was significant correlation between COV19-QoL and age, time since first infected and perceived health score (p<0.05). Conclusion: Aging, low education, existing chronic conditions, hospitalization, number of long symptoms, continuation of symptoms, and perception of health were risky factors for impact of the pandemic on quality of life. Specific rehabilitation services and programmes seems to be urgent need in overcoming this issue and to improve health. Key Words (MeSH Terms): Long COVID; COVID-19; quality of life; adults; family health

A survey of Iranian population attitude about vaccination against COVID-19 and evaluation of its spontaneous reporting of adverse effects (preprint)

Abstract Objectives: The COVID-19 pandemic continues to claim victims around the world, and Iran is no exception from this ravage. Vaccine development led to growing optimism regarding control of COVID-19. Vaccine acceptance by the majority of the population is important for the success in controlling COVID-19. This study assessed the attitude of Iranian population toward COVID-19 vaccination. Also, the adverse effects of the COVID-19 vaccines on vaccinated individuals were reported. Method: This cross-sectional study was conducted from May to July 2021 among Iranian population. The data was collected using the online researcher-made questionnaire. The questionnaire contained 16 questions in 3 sections. Results: The questionnaire was filled out by 916 people in total. The majority of participants had 40-65 years old (N:480, 52.4%). More than half of participants were from health care team (N:543, 59.3%). The majority of participants trusted the vaccine and said they would inject it (N:582, 63.5%). However more than 80% of participants preferred non-domestic vaccines over Iranian ones. Potential adverse effect following vaccination was the main concern of responders (N:576, 62.9%). The most common adverse effects reported by vaccine recipients were temporary fatigue and muscle pain (N:313, 71.95%). The level of education, academic area and area of practice in the health system were significantly associated with the positive response to COVID-19 vaccination (P-value 0.0001, 0.0001 and 0.004 respectively). Conclusion: According to the results of this study, Iranian health authorities should provide clear information about the safety and efficacy of COVID-19 vaccines, especially domestic types, to increase public confidence and awareness regarding vaccines.

WHAT THE COVID-19 PANDEMIC TAUGHT US IN CHILDREN (preprint)

Objective: The COVID-19 pandemic is an important cause of morbidity and mortality, which has had a negative impact worldwide. We aimed to contribute to the medical literature by sharing the knowledge and experience of pediatric patients who were diagnosed as having COVID-19 in a one-year period. Method: Patients aged 1 month to 18 years who were diagnosed as having COVID-19 in our clinic, between March 2020 and April 2020, from when COVID-19 was declared as a pandemic, were included in the study. Results: Four hundred sixty-seven children were included in the study. There were 34 (7.3%) patients under one year of age, 111 (23.8%) between 1-5 years, 98 (30.4%) between 5-10 years, 142 (30.4%) between 11-15 years, and 82 (17.6%) age over 15 years. Fever (88.2%), vomiting (32.4%), and diarrhea (29.4%) in patients aged under 1 year, sore throat (36.6%) in patients aged 11-15 years, and dysgeusia (11%), anosmia (14.6%), headache (18.3%), malaise (40.8%), myalgia (28%), and dyspnea (17.1%) in those aged over 15 years of age were found significantly more common compared with the other age groups. Thirty-five (7.5%) patients were asymptomatic, 365 (78.1%) had mild disease, 35 (7.5%) were moderate, 27 (5.8%) were severe, and five (1.07%) were critical. Leukocyte count, erythrocyte sedimentation rate, ferritin, and C-reactive protein values were significantly higher in hospitalized patients. Four patients died during the study period (0.8%, 4/494). Conclusion: Although COVID-19 has an asymptomatic and mild course in children, it should be kept in mind that it may have a severe course.

CLUSTER ANALYSIS IDENTIFIES LONG COVID SUBTYPES IN BELGIAN PATIENTS (preprint)

SARS CoV-2 infection presents complications known as long Covid, a multisystemic organ disease which allow multidimensional analysis. ObjectivesThis study aims to identify Long Covid clusters and to relate them to the clinical classification devised at the Clinical Research Unit of Brugmann University Hospital, Brussels. MethodA two-stage multidimensional exploratory analysis was performed on a cohort of 205 long Covid patients, involving a Factorial Analysis of Mixed Data (FAMD), and then Hierarchical Clustering Post Component Analysis (HCPC). ResultsThe studys sample comprised 76% women, with an average age of 44.5 years. Three clinical forms were identified: long, persistent, and post-viral syndrome. Multidimensional analysis identified three clusters: cluster 1 (myalgia-like pain) associated with the persistent clinical form; cluster 2 (neurocognitive disorders) linked to the long clinical form; cluster 3 (neurocognitive disorders, anxio-depressive syndrome, joint pain and myalgia, peripheral nervous system disorders with dysautonomia, including Postural Orthostatic Tachycardia Syndrome, along with digestive system disorders). However, biological data did not provide sufficient differentiation between the clusters. ConclusionLong Covid phenotypes, as well as clinical forms, appear to be associated with distinct pathophysiological mechanisms or genetic predisposition, warranting further investigation.

Safety and immunogenicity of VLPCOV-02, a SARS-CoV-2 self-amplifying RNA vaccine with a modified base, 5-methylcytosine, in healthy individuals (preprint)

Continuing emergence of variants of concern resulting in reduced SARS-CoV-2 vaccine efficacy necessitates additional prevention strategies. The structure of VLPCOV-01, a lipid nanoparticle-encapsulated, self-amplifying RNA COVID-19 vaccine with a comparable immune response to BNT162b2, was revised by incorporating a modified base, 5-methylcytosine to reduce reactogenicity, and an updated receptor-binding domain derived from Brazil (gamma) variant. Interim analyses of a phase 1 dose-escalation booster vaccination study with the resulting construct, VLPCOV-02, in healthy, previously vaccinated Japanese individuals (N=96) are reported (jRCT2051230005). A dose-related increase in solicited local and systemic adverse events was observed, which were generally rated mild or moderate. The most commonly occurring events were tenderness, pain, fatigue, and myalgia. Serum SARS-CoV-2 immunoglobulin titers increased during the 4 weeks post-immunization. VLPCOV-02 demonstrated a favorable safety profile compared with VLPCOV-01, with a lower frequency of adverse events and fewer fever events at an equivalent dose. These findings support further study of VLPCOV-02.

The well-being and work-related stress of senior school leaders in Wales and Northern Ireland during the COVID-19 pandemic: A cross-sectional descriptive study (preprint)

The COVID-19 pandemic caused far-reaching societal changes, including significant educational impacts, affecting over 1.6 billion pupils and 100 million education practitioners globally. Senior school leaders were at the forefront; an occupation already reporting high work-related stress and large numbers leaving the profession preceding COVID-19, leaders were exposed to high demands relating to the numerous challenges they had to manage during a "crisis leadership" period. This cross-sectional descriptive study conducted through through the international COVID-HL network aimed to examine the well-being and work-related stress of senior school leaders (n=323) in Wales (n=172) and Northern Ireland (n=151) during COVID-19 (2021-2022). Findings suggest that senior school leaders reported high workloads (54.22{+/-}11.30 hours/week), low well-being (65.2% n=202, mean WHO-5 40.85{+/-}21.57), depressive symptoms (WHO-5 34.8% n=108) and high work-related stress (PSS-10: 29.91{+/-}4.92). High exhaustion (BAT: high/very high 89.0% n=285) and specific psychosomatic complaints (experiencing muscle pain 48.2% n=151) were also reported, and females had statistically higher outcomes in these areas. School leaders were engaging in self-endangering working behaviours; 74.7% (n=239) gave up leisure activities in favour of work and 63.4% (n=202) sacrificed sufficient sleep, which was statistically higher for females. These findings are concerning given that the UK is currently experiencing a "crisis" in educational leadership against a backdrop of pandemic-related pressures. Senior leaders high attrition rates further exacerbate this, proving costly to educational systems and placing additional financial and other pressures on educational settings and policy response. This has implications for senior leaders and pupil-level outcomes including health, well-being and educational attainment, requiring urgent tailored and targeted support from the education and health sectors. This is particularly pertinent for Wales and Northern Ireland as devolved nations in the UK, who are both implementing or contemplating major education system level reforms, including new statutory national curricula, requiring significant leadership, engagement and ownership from the education profession.

A mixture of essential oils from three Cretan Aromatic Plants inhibits SARS-CoV-2 proliferation: A Proof-of-Concept intervention study in ambulatory patients (preprint)

Introduction: The need for therapeutic regimens for non-critically ill patients during the COVID-19 pandemic remains unmet. Previous work has shown that a combination of three aromatic plants’ essential oil (CAPeo) (Thymbra capitata (L.) Cav., Origanum dictamnus L., Salvia fruticosa Mill.) has remarkable in vitro antiviral activity. Given its properties, it was urgent to explore its potential in treating mild COVID-19 patients in primary care. Methods: 69 adult patients were included in a clinical, Proof-of-Concept (PoC) intervention study. Family physicians implemented the observational study in two arms (intervention and control group) during three study periods (IG2020, n=13, IG2021/22, n=25 and CG2021/22, n=31). The SARS-CoV-2 infection was confirmed by real-time PCR. The CAPeo mixture, was administered daily for 14 days, per os in the intervention group, while the control group received usual care. Results: The PoC study, found that the number and frequency of general symptoms, including general fatigue, weakness, fever and myalgia, decreased following CAPeo administration. The average presence (number) of symptoms decreased in IG (4.7 to 1.4) as well as in CG (4.0 to 3.1) by Day 7 compared to Day 1, representing a significant decrease in cumulative presence in IC (-3.3 vs. -0.9, p<0.001; η2=0.20) on Day 7 and on Day 14 (-4.2 vs. -2.9, p=0.027; η2=0.08). Discussion/Conclusion: Our findings suggest that CAPeo, possesses potent antiviral activity, in addition tο the Influenza A and B and the human rhinovirus HRV14 strains against SARS-CoV-2. The early and effective impact in alleviating key symptoms of COVID-19 may suggest this mixture can act as a complementary natural agent for mild COVID-19 patients

Prevalence of Post COVID-19 Condition among healthcare workers: self-reported online survey in four African countries (preprint)

The impact of Post COVID-19 Condition is ongoing despite the declaration that the COVID-19 pandemic has ended. In this study, we explore the prevalence of PCC among healthcare workers (HCWs) in four African Countries and its influence on their professional performance. This study was conducted as an online cross-sectional survey of healthcare workers from four African countries (Cameroon, Egypt, Nigeria, and Somalia) between the 20th of December 2021 to 12th of January 2022. We determined the prevalence of PCC based on the WHO case definition and assessed variables associated with a higher prevalence of PCC in these countries using univariable and multivariable logistic regression analyses. A total of 706 HCWs from four African countries were included in this survey. Most of the HCWs were aged between 18-34 years (75.8%, n=535). Our findings showed that 19.5% (n=138) of the HCWs had tested positive for SARS-CoV-2. However, 8.4% (n=59) were symptomatic for COVID-19 but tested negative or were never tested. Two-thirds of the HCWs (66.4%, n=469)have received a COVID-19 vaccine and 80.6% (n=378) of those vaccinated had been fully vaccinated. The self-reported awareness rate of PCC among the HCWs was 16.1% (n=114/706) whereas the awareness rate of PCC among COVID-19-positive HCWs was 55.3 % (n=109/197). The prevalence of PCC among HCWs was 58.8% (n=116). These changes include the self-reported symptoms of PCC which included headache (58.4%, n=115), fatigue (58.8%, n=116), and muscle pain (39.6%, n=78). Similarly, 30% (n=59) and 20.8% (n=41) of the HCWs reported the loss of smell and loss of taste long after their COVID-19 infection, respectively. Some HCWs (42%, n=83) believed that their work performance has been affected by their ongoing symptoms of PCC. There was no significant difference in the prevalence of PCC among the vaccinated and unvaccinated HCWs (p > 0.05). Of the socio-demographic variables, age (older HCWs between 45-54 years; OR:1.7; 95% CI: 1.06, 10.59; p = 0.001) and location (Egypt; OR:14.57; 95% CI: 2.62, 26.76; p = 0.001) were more likely to have experienced PCC than other age groups and countries respectively. The study revealed low prevalence of PCC among the surveyed HCC. In addition, it observed the need for adequate medical and psychological support to HCWs with PCC, improve their COVID-19 vaccination uptake, and conduct mass advocacy campaigns on PCC.

The Role of VSL#3 in the Treatment of Fatigue and Other Symptoms in Long Covid-19 Syndrome: a Randomized, Double-blind, Placebo-controlled Pilot Study (DELong#3) (preprint)

Long COVID, also known as Post-acute COVID-19 Syndrome (PACS), is a chronic condition affecting individuals who have recovered from acute COVID-19. It is currently estimated that around 65 million people worldwide suffer from Long COVID. It is characterized by a range of symptoms, including fatigue, exertion intolerance, neurocognitive and sensory impairment, sleep disturbance, myalgia/arthralgia, and dysautonomia. Among them fatigue has emerged as a burdensome and pervasive issue, significantly impacting the quality of life and daily functioning of Long COVID patients. Alterations in the composition of the intestinal microbiota has been reported in COVID-19 patients. Dysbiosis persists even after several months of recovery from acute SARS-CoV-2 infection. Based on this evidence, we carried out a phase 3, randomized, double-blind, placebo-controlled trial aimed at evaluating the efficacy of VSL#3, a consortium of probiotic bacterial strains, in reducing fatigue and improving various aspects of patients' well-being in patients with Long COVID syndrome.

Immunological responses and adverse reactions of the heterologous second booster dose of BNT162b2 after two-dose CoronaVac for COVID-19 vaccination in healthcare workers of Faculty of Medicine, Naresuan University.

BACKGROUND: The first COVID-19 vaccination campaign in Thailand began in April 2020, with healthcare workers receiving two doses of inactivated COVID-19 vaccine (CoronaVac). However, the emergence of the delta and omicron variants raised concerns about vaccine effectiveness. The Thai Ministry of Public Health provided the first booster dose (third dose) and second booster dose (fourth dose) of the mRNA vaccine (BNT162b2) for healthcare workers. This study investigated the immunity and adverse reactions elicited by a heterologous second booster dose of BNT162b2 after a two-dose CoronaVac vaccination for COVID-19 in healthcare workers of the Faculty of Medicine, Naresuan University. METHODS: IgG titres against the SARS-CoV-2-spike protein were measured four and 24 weeks after the second booster dose of BNT162b2 in the study participants. Adverse reactions were recorded during the first three days, four weeks and 24 weeks after the second booster dose of BNT162b2. RESULTS: IgG against the SARS-CoV-2-spike protein was positive (>10 U/ml) in 246 of 247 participants (99.6 %) at both four and 24 weeks after the second booster dose of BNT162b2. The median specific IgG titres at four and 24 weeks after the second booster dose of BNT162b2 were 299 U/ml (min: 2, max: 29,161) and 104 U/ml (min: 1, max: 17,920), respectively. The median IgG level declined significantly 24 weeks after the second booster dose of the BNT162b2 vaccine. Of the 247 participants, 179 (72.5 %) experienced adverse reactions in the first three days after the second booster dose of BNT162b2. Myalgia, fever, headache, injection site pain and fatigue were the most common adverse reactions. CONCLUSION: This study demonstrated that a heterologous second booster dose of BNT162b2 after two doses of CoronaVac induced elevated IgG against the SARS-CoV-2-spike protein and caused minor adverse reactions in healthcare workers of the Faculty of Medicine, Naresuan University. This study was registered as Thailand Clinical Trials No. TCTR20221112001.

Myositis developing after Covid-19 mRNA vaccine: Case Report.

Vaccine-related side effects are common. Usually, pain, edema, redness and tenderness may be seen at the injection site. Symptoms such as fever, fatigue, myalgia may occur. The coronavirus 2019 disease (Covid-19) has affected many people around the world. Although the vaccines that have been used play an active role in the fight against the pandemic, adverse events still continue to be reported. We present a 21-year-old patient who was diagnosed as having myositis after receiving covid vaccine with complaints of pain in her left arm two days after the 2nd dose of BNT162b2 mRNA Covid-19 vaccine, followed by inability to stand up from sitting and squatting and difficulty in going up and down stairs. Keywords: vaccine, myositis, creatine kinase, IVIG.

Long COVID brain fog and muscle pain are associated with longer time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute infection.

Introduction: The incidence of long COVID is substantial, even in people with mild to moderate acute COVID-19. The role of early viral kinetics in the subsequent development of long COVID is largely unknown, especially in individuals who were not hospitalized for acute COVID-19. Methods: Seventy-three non-hospitalized adult participants were enrolled within approximately 48 hours of their first positive SARS-CoV-2 RT-PCR test, and mid-turbinate nasal and saliva samples were collected up to 9 times within the first 45 days after enrollment. Samples were assayed for SARS-CoV-2 using RT-PCR and additional SARS-CoV-2 test results were abstracted from the clinical record. Each participant indicated the presence and severity of 49 long COVID symptoms at 1-, 3-, 6-, 12-, and 18-months post-COVID-19 diagnosis. Time from acute COVID-19 illness onset to SARS-CoV-2 RNA clearance greater or less than 28 days was tested for association with the presence or absence of each of 49 long COVID symptoms at 90+ days from acute COVID-19 symptom onset. Results: Self-reported brain fog and muscle pain at 90+ days after acute COVID-19 onset were negatively associated with viral RNA clearance within 28 days of acute COVID-19 onset with adjustment for age, sex, BMI ≥ 25, and COVID vaccination status prior to COVID-19 (brain fog: aRR 0.46, 95% CI 0.22-0.95; muscle pain: aRR 0.28, 95% CI 0.08-0.94). Participants reporting higher severity brain fog or muscle pain at 90+ days after acute COVID-19 onset were less likely to have cleared SARS-CoV-2 RNA within 28 days. The acute viral RNA decay trajectories of participants who did and did not later go on to experience brain fog 90+ days after acute COVID-19 onset were distinct. Discussion: This work indicates that at least two long COVID symptoms - brain fog and muscle pain - at 90+ days from acute COVID-19 onset are specifically associated with prolonged time to clearance of SARS-CoV-2 RNA from the upper respiratory tract during acute COVID-19. This finding provides evidence that delayed immune clearance of SARS-CoV-2 antigen or greater amount or duration of viral antigen burden in the upper respiratory tract during acute COVID-19 are directly linked to long COVID. This work suggests that host-pathogen interactions during the first few weeks after acute COVID-19 onset have an impact on long COVID risk months later.